Ketamine's antidepressant effect is mediated by energy metabolism and antioxidant defense system.

Fewer than 50% of all patients with major depressive disorder (MDD) treated with currently available antidepressants (ADs) show full remission. Moreover, about one third of the patients suffering from MDD does not respond to conventional ADs and develop treatment-resistant depression (TRD). Ketamine, a non-competitive, voltage-dependent N-Methyl-D-aspartate receptor (NMDAR) antagonist, has been shown to have a rapid antidepressant effect, especially in patients suffering from TRD. Hippocampi of ketamine-treated mice were analysed by metabolome and proteome profiling to delineate ketamine treatment-affected molecular pathways and biosignatures. Our data implicate mitochondrial energy metabolism and the antioxidant defense system as downstream effectors of the ketamine response. Specifically, ketamine tended to downregulate the adenosine triphosphate (ATP)/adenosine diphosphate (ADP) metabolite ratio which strongly correlated with forced swim test (FST) floating time. Furthermore, we found increased levels of enzymes that are part of the 'oxidative phosphorylation' (OXPHOS) pathway. Our study also suggests that ketamine causes less protein damage by rapidly decreasing reactive oxygen species (ROS) production and lend further support to the hypothesis that mitochondria have a critical role for mediating antidepressant action including the rapid ketamine response

Analisa Pondasi Pile Raft Pada Tanah Lunak Dengan Plaxis 2d

Permasalahan penurunan menjadi salah satu masalah yang sering dihadapi para perencana pondasi bangunan dikarenakan oleh kondisi tanah yang lunak. Untuk mengatasi permasalahan yang ada, banyak perencana menggunakan pondasi raft atau pondasi rakit, karena dianggap mampu memberikan faktor keamanan yang memadai dalam menghadapi kegagalan daya dukung ultimate. Namun diperkirakan pondasi raft ini akan mengalami penurunan yang besar. Permasalahan tersebut mungkin dapat berkurang jika adanya penambahan pile pada pondasi raft sehingga menjadi pondasi pile raft. Dengan penambahan pile pada pondasi raft diharapkan perencanaannya mempertimbangkan segi ekonomis. Dengan menggunakan beban merata 6 t/m2, dilakukan penelitian pada pondasi pile raft dengan memvariasikan tebal raft yakni 80 cm, 100 cm, 120 cm dan 140 cm. Untuk panjang pile divariasikan dari panjang 5 m, 7 m, 9 m, 13 m dan 15 m. Analisis penurunan dilakukan dengan menggunakan software Plaxis 2D dan Metode Poulos. Hasil dari penelitian ini menunjukkan bahwa Penambahan jumlah pile pada pondasi raft menghasilkan profil penurunan yang berkurang namun pada suatu keadaan tertentu penambahan pile tidak memberikan kontribusi yang lebih signifikan. Begitupun dengan perhitungan Poulos, pada konfigurasi pile tertentu tidak memberi kontribusi lagi. Sehingga desain yang ekonomis pada penelitian ini adalah dengan menggunakan tebal raft 80 cm dengan panjang pile 13 m dan konfigurasi pile 7x7

Stress-primed secretory autophagy promotes extracellular BDNF maturation by enhancing MMP9 secretion

The stress response is an essential mechanism for maintaining homeostasis, and its disruption is implicated in several psychiatric disorders. On the cellular level, stress activates, among other mechanisms, autophagy that regulates homeostasis through protein degradation and recycling. Secretory autophagy is a recently described pathway in which autophagosomes fuse with the plasma membrane rather than with lysosomes. Here, we demonstrate that glucocorticoid-mediated stress enhances secretory autophagy via the stress-responsive co-chaperone FK506-binding protein 51. We identify the matrix metalloproteinase 9 (MMP9) as one of the proteins secreted in response to stress. Using cellular assays and in vivo microdialysis, we further find that stress-enhanced MMP9 secretion increases the cleavage of pro-brain-derived neurotrophic factor (proBDNF) to its mature form (mBDNF). BDNF is essential for adult synaptic plasticity and its pathway is associated with major depression and posttraumatic stress disorder. These findings unravel a cellular stress adaptation mechanism that bears the potential of opening avenues for the understanding of the pathophysiology of stress-related disorders

MOESM4 of Rapid in situ 13C tracing of sucrose utilization in Arabidopsis sink and source leaves

Additional file 4: Figure S2. Simultaneous labeling of vascular tissue by co-feeding of 6-Carboxyfluorescein diacetate (green fluorescence) and Calcofluor White (blue fluorescence) dissolved in tap water. The fluorescent dyes were fed through the petiole of a transition leaf. A. thaliana plants were grown on soil under 8 h short day conditions and analysed at developmental stage 1.10–1.15. (A) Bright-field image of an approximately longitudinal optical section obtained by a confocal laser scanning microscope. The arrow indicates the position of a xylem vessel. (B) Phloem tissue indicated by 6-Carboxyfluorescein flourescence using excitation wave length λ = 488 nm and emission filter λ = 560 nm (green). (C) Xylem and apoplastic continuum indicated by Calcofluor White fluorescence using excitation wave length λ = 355 nm and an emission filter λ = 425 nm (blue). (D) Merged images (A–C)

Paroxetine Administration Affects Microbiota and Bile Acid Levels in Mice.

Recent interest in the role of microbiota in health and disease has implicated gut microbiota dysbiosis in psychiatric disorders including major depressive disorder. Several antidepressant drugs that belong to the class of selective serotonin reuptake inhibitors have been found to display antimicrobial activities. In fact, one of the first antidepressants discovered serendipitously in the 1950s, the monoamine-oxidase inhibitor Iproniazid, was a drug used for the treatment of tuberculosis. In the current study we chronically treated DBA/2J mice for 2 weeks with paroxetine, a selective serotonin reuptake inhibitor, and collected fecal pellets as a proxy for the gut microbiota from the animals after 7 and 14 days. Behavioral testing with the forced swim test revealed significant differences between paroxetine- and vehicle-treated mice. Untargeted mass spectrometry and 16S rRNA profiling of fecal pellet extracts showed several primary and secondary bile acid level, and microbiota alpha diversity differences, respectively between paroxetine- and vehicle-treated mice, suggesting that microbiota functions are altered by the drug. In addition to their lipid absorbing activities bile acids have important signaling activities and have been associated with gastrointestinal diseases and colorectal cancer. Antidepressant drugs like paroxetine should therefore be used with caution to prevent undesirable side effects

Paroxetine Administration Affects Microbiota and Bile Acid Levels in Mice.

Recent interest in the role of microbiota in health and disease has implicated gut microbiota dysbiosis in psychiatric disorders including major depressive disorder. Several antidepressant drugs that belong to the class of selective serotonin reuptake inhibitors have been found to display antimicrobial activities. In fact, one of the first antidepressants discovered serendipitously in the 1950s, the monoamine-oxidase inhibitor Iproniazid, was a drug used for the treatment of tuberculosis. In the current study we chronically treated DBA/2J mice for 2 weeks with paroxetine, a selective serotonin reuptake inhibitor, and collected fecal pellets as a proxy for the gut microbiota from the animals after 7 and 14 days. Behavioral testing with the forced swim test revealed significant differences between paroxetine- and vehicle-treated mice. Untargeted mass spectrometry and 16S rRNA profiling of fecal pellet extracts showed several primary and secondary bile acid level, and microbiota alpha diversity differences, respectively between paroxetine- and vehicle-treated mice, suggesting that microbiota functions are altered by the drug. In addition to their lipid absorbing activities bile acids have important signaling activities and have been associated with gastrointestinal diseases and colorectal cancer. Antidepressant drugs like paroxetine should therefore be used with caution to prevent undesirable side effects